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Selenium-containing thioredoxin reductase inhibitor ethaselen sensitizes non-small cell lung cancer to radiotherapy.
MedLine Citation:
PMID:  21562407     Owner:  NLM     Status:  Publisher    
It has been proposed that thioredoxin reductase (TR) is a mediator that allows non-small cell lung cancer (NSCLC) to develop resistance to irradiation; however, little is known regarding the detailed mechanisms of action. Thus, ethaselen {1, 2-[bis (1,2-benzisoselenazolone-3 (2H)-ketone)] ethane, BBSKE}, a novel organoselenium TR inhibitor, is currently being investigated in a phase I clinical trial in China. However, its radiosensitizing effect remains unexplored. In this study, we found that the activity of TR increased dramatically in both A549 and H1299 cells after radiation, and moreover, could be inhibited by pretreatment with BBSKE (5 μmol/l). As a TR inhibitor, BBSKE enhanced the efficacy of radiation therapy both in vivo and in vitro without observable toxicity. BBSKE was found to suppress irradiation-induced NF-κB activation dramatically when using A549 cells stably transfected with NF-κB luciferase reporter. These results show the critical role of TR in the radioresistance of NSCLC and suggest that BBSKE is a potentially promising agent for the treatment of patients with NSCLC clinically.
Lei Wang; Jia-Ning Fu; Jing-Yu Wang; Cun-Jing Jin; Xiao-Yuan Ren; Qiang Tan; Jing Li; Han-Wei Yin; Kun Xiong; Tian-Yu Wang; Xin-Min Liu; Hui-Hui Zeng
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-5-10
Journal Detail:
Title:  Anti-cancer drugs     Volume:  -     ISSN:  1473-5741     ISO Abbreviation:  -     Publication Date:  2011 May 
Date Detail:
Created Date:  2011-5-12     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9100823     Medline TA:  Anticancer Drugs     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
aPeking University First Hospital bState Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences cCollege of Life Sciences, Peking University dSchool of Pharmaceutical Sciences, Peking University Health Science Center, Beijing, China.
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